Although a considerable amount of literature has accrued on the effects of heat on the immune system, the role of this interaction in cancer therapy by hyperthermia, whether positive or negative, remains unclear. The strongest argument to date supporting the importance of this interaction is the evidence of abscopal regression of metastases and untreated tumor areas after hyperthermia treatment, while histological studies show evidence of extensive infiltration of tumors by host immune cells following hyperthermia. Comparison of tumor cell survival and tumor cure reveals that direct cell killing by heat, although an important factor cannot completely account for tumor cure. Thus some host mechanism, possibly damage to tumor blood supply or enhancement of the immune response, must be involved. We intend to investigate the effect of hyperthermia on the role of mononuclear phagocytes in the host immune response to cancer by determining: 1) the effects of these modalities on the kinetics of macrophage and lymphocyte infiltration into tumors; 2) the effects of heat treatment on the production of macrophage growth factor (MGF) by cells derived from the tumor and on the proliferative activity of intra-tumor macrophages; 3) the effects of hyperthermia on the production of macrophage activating factor (MAF) and on the tumoricidal activity of intra-tumor macrophages and whether this activity can be modified or enhanced; 4) the kinetics of these various steps in the host immune response after treatment (e.g., how does the immune response recover with time if it is suppressed); and 5) the differences in host immune response in the above determinations to heat either locally applied or given whole body. Flow cytometry will be used to separate the cell populations of interest in this study. We believe an important place to study this host defense to cancer is in the tumor itself, yet relatively little work has been reported. We strongly believe these basic studies will provide new fundamental approaches to the immunotherapy of cancer and further our understanding of the interaction between the immune response and hyperthermia for the treatment of cancer.